Effect of amiodarone and desethylamiodarone on choline uptake and phosphatidylcholine biosynthesis in cultured chick cardiac myocytes.
The objective of the study was to examine the hypothesis that amiodarone and its major metabolite desethylamiodarone alter choline uptake and metabolism in cardiac myocytes. Myocardial cells were obtained from 7-day-old chick embryos and were maintained in culture. Choline uptake, examined using [methyl 3H] choline, involves saturable and non-saturable processes. Amiodarone and desethylamiodarone at 10(-6) to 10(-4) M produced a significant (P less than 0.05) dose dependent reduction in choline uptake and inhibited the specific or carrier-mediated uptake process. The highest concentrations of each of these agents profoundly reduced choline uptake. Pulse chase experiments using [methyl 3H] choline showed that after a 2-h incubation with choline, about 85% of the label was recovered in phosphocholine, with the majority of the rest in phospholipid that was mainly phosphatidylcholine. Amiodarone and desethylamiodarone did not produce relevant alterations in choline metabolism namely phosphatidylcholine biosynthesis as neither drug altered the rate of disappearance of the label from phosphocholine or the appearance in phospholipid. Amiodarone but not desethylamiodarone produced a small but significant (P less than 0.05) increase in the amount of label that accumulated in CDP choline. These data demonstrate that amiodarone and desethylamiodarone decrease choline uptake into cardiac cells that may potentially be involved in either the mechanism of action or toxicity of amiodarone.
Rabkin
S W
SW
University of British Columbia, Vancouver, Canada.
D000638:Amiodarone / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002794:Choline / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis
D010713:Phosphatidylcholines; C036116:desethylamiodarone; D000638:Amiodarone; D002794:Choline